Can indapamide cause hyponatremia (low sodium levels)?

Indapamide Can Cause Hyponatremia (Low Sodium)

Yes, indapamide can definitely cause hyponatremia (low sodium levels), and this is documented as a significant adverse effect in both drug labeling and clinical guidelines.

Mechanism and Risk

Indapamide is a thiazide-like diuretic that works by inhibiting sodium reabsorption in the distal convoluting tubule. This mechanism can lead to:

• Excessive sodium excretion leading to hyponatremia
• Concurrent hypokalemia (low potassium) often accompanies the hyponatremia
• Impaired free water excretion contributing to dilutional hyponatremia

The FDA drug label specifically warns about this risk, stating that "severe cases of hyponatremia, accompanied by hypokalemia have been reported with recommended doses of indapamide" 1. This appears to be dose-related, with higher risk at 2.5 mg and 5 mg doses compared to the 1.25 mg dose.

Risk Factors

Certain patients are at higher risk for indapamide-induced hyponatremia:

• Elderly patients, particularly females 1, 2
• Lower body weight individuals
• Patients on higher doses (2.5 mg or 5 mg versus 1.25 mg)
• Patients with pre-existing electrolyte abnormalities
• Patients with liver cirrhosis 3

Clinical Presentation

Hyponatremia from indapamide can:

• Develop rapidly (within 2-6 weeks of starting therapy) 4, 5
• Be severe (serum sodium as low as 100-104 mmol/L has been reported) 4, 5
• Present with neurological symptoms including:
  • Delirium
  • Unsteady gait
  • Altered mental status
  • Seizures in severe cases

Prevention and Monitoring

To minimize the risk of indapamide-induced hyponatremia:

• Start with the lowest effective dose (1.25 mg) 1
• Monitor serum electrolytes (sodium, potassium, magnesium) regularly, especially:
  • Within the first few weeks of starting therapy
  • After dose adjustments
  • In high-risk patients (elderly, females)
• Be vigilant for early symptoms of hyponatremia

Management of Indapamide-Induced Hyponatremia

If hyponatremia develops:

1. Discontinue indapamide
2. For severe symptomatic hyponatremia (sodium <125 mmol/L with neurological symptoms):
   • Consider hypertonic (3%) saline administration with careful monitoring
   • Correct sodium slowly (no more than 8 mmol/L per day) to avoid central pontine myelinolysis 3
3. For hypovolemic hyponatremia (common with diuretics):
   • Volume expansion with normal saline
   • Correction of the underlying cause 3

Comparison to Other Diuretics

Indapamide is listed in clinical guidelines as a thiazide-like diuretic used in heart failure management 3. While all thiazide and thiazide-like diuretics can cause hyponatremia, case reports suggest that indapamide may cause particularly severe cases 4, 5, 2.

Clinical Implications

When prescribing indapamide:

• Use the lowest effective dose (1.25 mg when possible)
• Implement regular electrolyte monitoring
• Educate patients about symptoms of hyponatremia
• Consider alternative antihypertensives in high-risk patients
• Be aware that hyponatremia can be mistaken for syndrome of inappropriate antidiuretic hormone secretion (SIADH) 4

In conclusion, clinicians should maintain a high index of suspicion for hyponatremia in patients taking indapamide, particularly elderly females and those on higher doses.